The major objective of this research project is to delineate the genetic, environmental and phenotypic characteistics of major gene susceptibility to a wide variety of teratogens resulting in congenital craniofacial malformations, particularly facial clefting. Since the major gene under study is assumed to be either at the major histocompatibility complex (H-2 in mice, HLA in man) per se, or at some closely linked locus, congenic resistant pairs of mice are being utilized. The research will provide: (1) an assessment of the relative influence of the maternal and fetal haplotypes with respect to susceptibility (2) a determination of whether relative susceptibility and/or resistance to teratogen-induced congenital malformations is associated with genes at the K-end or D-end of the H-2 complex; (3) a determination of the qualitative and quantitative distribution in craniofacial embryonic tissues, under normal and teratogenic conditions, of H-2 antigens.